The present invention relates to pharmaceutical compositions, in particular to compositions containing an active ingredient having mucolytic or mucoregulating properties.
Carboxymethylthio acetic acid has been tested in rats against cancer by M. B. SAHASRABUDHE (Chemical Abstracts 67, 115647s (1967)).
Some of the acids and salts of carboxy alkylthio acetic acids of the formula EQU HOOC -- (CH.sub.2).sub.n -- S -- CH.sub.2 -- COOH (I)
in which n is 1 to 5 are known.
The acids of the above formula (I) and some salts are known per se and may be prepared by known processes. Thus, the preparation of acids in which n is 1, 2 or 3 is described by the following authors: N. Hellstrom, Zeitschr. Physik. Chim. (A), 157, 249 (1931), 163, 37, (1933); Larsson and Jonsson, Ber, 67, 759 (1934) and E. A. Fehnel, J. Am. Chem. Soc., 74, 1569-74 (1952). A synthetic route consists of reacting mercapto acetic acid with a halogenated carboxylic acid of the formula: EQU X -- (CH.sub.2).sub.n -- COOH
wherein X represents a halogen atom such as chlorine, bromine or iodine and n is 1, 2 or 3.
In practice a derivative of the appropriate halogenated carboxylic acid such as an alkali metal salt or an ester, in aqueous alkaline solution, or in absolute alcohol in the presence of sodium ethanolate is used. The temperature employed may be of the order of 25.degree. C for 30 to 60 minutes, followed by heating of the reaction mixture under reflux for one hour. Where the reaction product is a salt or ester the free acid can be obtained by conventional methods using an acid such as hydrochloric acid or sulphuric acid. The yields are usually of the order of 70 to 80%.
Certain compounds can be characterized as:
(Carboxymethylthio)acetic acid HOOC--CH.sub.2 --S--CH.sub.2 --COOH, called compound LJ 638 hereinafter, melting at 129.degree.-130.degree. C.
(Carboxyethylthio)acetic acid HOOC--CH.sub.2 --CH.sub.2 --S--CH.sub.2 --COOH, called compound LJ 629 hereinafter, melting at 94.degree. C.
(Carboxypropylthio)acetic acid HOOC--CH.sub.2 --CH.sub.2 --CH.sub.2 --S--CH.sub.2 --COOH, called compound LJ 630 hereinafter, melting at 74.degree. C.
(Carboxybutylthio)acetic acid HOOC--(CH.sub.2).sub.4 --S--CH.sub.2 --COOH, of which the preparation is described by M. S. Rabinovich et al. Zh. Obshch. Khim. 32, 1167-72 (1972), melting at 57.degree. C.
(Carboxypentylthio)acetic acid HOOC--(CH.sub.2).sub.5 --S--CH.sub.2 COOH, of which the preparation is described by Horst Remane et al., J. Prakt. Chem. 312, (6), 1058-62 (1970), melting at 86.degree. C.